Crosstalk between Tumor-Infiltrating Immune Cells and Cancer-Associated Fibroblasts in Tumor Growth and Immunosuppression of Breast Cancer

Soongsathitanon, Jarupa; Jamjuntra, Pranisa; Sumransub, Nuttavut; Yangngam, Supaporn; Fuente, Marjorie De la; Landskron, Glauben; Thuwajit, Peti; Hermoso, Marcela A.; Thuwajit, Chanitra

doi:10.1155/2021/8840066

Cited by 18 publications

(14 citation statements)

References 169 publications

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“…Patients with luminal subtype breast cancer with an active immune system have a longer survival time than those with an inactive immune system (30). An active immune system in the tumour environment could increase the antitumour immunity, which will then eliminate the tumour (31). As an immune adhesion molecule, CD58 can mediate the cytotoxicity of lymphokine-activated killing and natural killer cells (32) in neuroblastoma, and may stimulate T-cell proliferation and augment cytotoxic Tlymphocyte (CTL) cytotoxicity in colorectal cancer (33).…”

Section: Discussionmentioning

confidence: 99%

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Xiong¹,

Motomura²,

Tamori³

et al. 2022

Anticancer Res

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Background/Aim: CD58 is an immune adhesion molecule on the cellular surface. It was previously found that a high expression of CD58 predicted a poor prognosis of patients with lower-grade gliomas. Therefore, the aim of this paper was to investigate the association between CD58 and breast cancer. Materials and Methods: CD58 gene expression data downloaded from cBioPortal was compared between the different subtypes of breast cancer. Clinical prognosis was examined using Kaplan-Meier analysis and multivariable Cox regression analysis. The association between CD58 expression and immune cell infiltration was estimated using the TIMER 2.0 web platform. Finally, the tumour sphere formation of aldehyde dehydrogenase 1 (ALDH1) high basallike breast cancer stem cells in which CD58 was knocked down using siRNA was measured. Results: CD58 mRNA was mainly enriched in claudin-low and basal-like subtypes. The high expression of CD58 predicted a good prognosis in patients with luminal A and luminal B breast cancer. This prediction may be due to the association of immune cell infiltration with CD58. Notably, patients with luminal A breast cancer with a high expression of CD58 in association with ALDH1A3 exhibited a good prognosis; however, this did not apply to patients with basal-like breast cancer. The in vitro experiments revealed that knockdown of CD58 inhibited the tumour sphere formation ability of ALDH1 high basal-like cancer cells. Conclusion: CD58 may function as a potential prognostic biomarker and therapeutic target in ALDHpositive basal-like cancer stem cells.According to the enumeration published in 2022, over 287,000 new cases of breast cancer have been estimated to be diagnosed in the United States each year, with breast cancer accounting for 31% of all cancers among females. In addition, over 43,000 women are estimated to succumb to the disease each year (1). Breast cancer is a heterogeneous disease which can be subtyped by predictive analysis of the microarrays 50 (PAM50) gene panel. Breast cancer PAM50 molecular subtypes include luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, basallike, normal-like and claudin-low. Luminal A and B subtypes are mainly associated with oestrogen receptor (ER) + cancers (2, 3), while the majority of triple-negative breast cancers (TNBCs) are also classified as claudin-low and basal-like subtypes (4).Based on the subtyping, treatment of breast cancer mainly entails surgery, radiotherapy, and drug therapy, including chemotherapy, endocrine therapy and molecular targeted therapy. In general, patients with luminal A breast cancer have a favourable prognosis owing to the effectiveness of anti-hormone receptor therapy (5). By contrast, patients with the basal-like subtype have an unfavourable prognosis due to resistance to conventional therapy (6). Therefore, there is 5223

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Section: Discussionmentioning

confidence: 99%

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Xiong¹,

Motomura²,

Tamori³

et al. 2022

Anticancer Res

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“…As is known to all, CAFs are crucial components in the tumor microenvironment, play pivotal roles in tumor progression, and further impact clinical prognosis ( Giorello et al, 2021 ). In breast cancer, CAFs can interact with tumor-infiltrating immune cells and promote tumor development and immunosuppression ( Gunaydin, 2021 ; Soongsathitanon et al, 2021 ). Together, these findings indicate that INHBA may potentially inhibit the immune response by regulating immune cell recruitment and activation in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of INHBA Is Correlated With Poor Prognosis and High Immune Infiltrating Level in Breast Cancer

Cheng

Liu

et al. 2022

Front. Bioinform.

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Background: Inhibin, beta A (INHBA) is a member of the transforming growth factor-β superfamily and is associated with carcinogenesis and cancer progression in several types of human cancers. However, its significance in breast cancer has not been evaluated. Here, we investigated the prognostic value of INHBA and its correlation with tumor-infiltration immune cells in the microenvironment of breast cancer.Methods: In this study, we analyzed the INHBA expression profile in the Oncomine database and Tumor Immune Estimation Resource 2.0 (TIMER2.0) site. Using Breast Cancer Gene-Expression Miner (bc-GenExMiner v4.7) tool and the UALCAN cancer database, we further evaluated the correlation of INHBA expression with clinicopathological factors in breast cancer. Then, we assessed the clinical prognostic value of INHBA using Kaplan–Meier Plotter and the PrognoScan databases. The correlations between INHBA and tumor-infiltrating immune cells were investigated via TIMER2.0. In addition, correlations between INHBA expression and gene markers of immune infiltrates were analyzed by TIMER2.0 and Gene Expression Profiling Interactive Analysis 2.Results: Compared with the level in normal tissues, the INHBA mRNA expression was upregulated in different subtypes of breast cancer, and its expression was positively correlated with progesterone receptor, human epidermal growth factor receptor-2 status, and PAM50 subtypes but negatively related to age and basal-like status. The INHBA protein was also highly expressed in primary breast cancer and closely related to the pathological stage. Patients with high INHBA expression levels showed worse overall survival, relapse-free survival, and distant metastasis-free survival. Also, high INHBA expression was significantly associated with worse overall survival and relapse-free survival in positive lymph nodes. Of interest, INHBA expression was negatively correlated with infiltrating levels of activated NK cells, NKT, and CD4+ T cells but was positively correlated with tumor infiltration of CD8+ T cells, neutrophils, especially macrophages and cancer-associated fibroblasts. Moreover, INHBA expression showed strong correlations with various markers of monocytes/macrophages and cancer-associated fibroblasts.Conclusion: High INHBA expression is correlated with poor prognosis and the infiltration of immune cells in the tumor microenvironment. These findings suggest that INHBA may be involved in immune escape and can serve as a potential biomarker of prognosis and tumor-infiltrating immune cells.

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“…In particular, MC1 produces IL-9, and histamine, which induces DC maturation and inhibits tumor growth in murine models. In contrast, MC2 produces a variety of angiogenic and metastatic substances, including VEGF, FGF, MMP9, TGFβ, and cytokines (IL-1β, IL-6, and IL-13) [111,112]. Importantly, MCs can also alter the anti-tumor immune response.…”

Section: Mcs and Cafsmentioning

confidence: 99%

Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions

Thiery

2022

Exploration of Targeted Anti-Tumor Therapy

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Cancer-associated fibroblasts (CAFs) are highly heterogeneous players that shape the tumor microenvironment and influence tumor progression, metastasis formation, and response to conventional therapies. During the past years, some CAFs subsets have also been involved in the modulation of immune cell functions, affecting the efficacy of both innate and adaptive anti-tumor immune responses. Consequently, the implication of these stromal cells in the response to immunotherapeutic strategies raised major concerns. In this review, current knowledge of CAFs origins and heterogeneity in the tumor stroma, as well as their effects on several immune cell populations that explain their immunosuppressive capabilities are summarized. The current development of therapeutic strategies for targeting this population and their implication in the field of cancer immunotherapy is also highlighted.

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Crosstalk between Tumor-Infiltrating Immune Cells and Cancer-Associated Fibroblasts in Tumor Growth and Immunosuppression of Breast Cancer

Cited by 18 publications

References 169 publications

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

High Expression ofCD58andALDH1A3Predicts a Poor Prognosis in Basal-like Breast Cancer

Increased Expression of INHBA Is Correlated With Poor Prognosis and High Immune Infiltrating Level in Breast Cancer

Modulation of the antitumor immune response by cancer-associated fibroblasts: mechanisms and targeting strategies to hamper their immunosuppressive functions

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